乳糖化-去甲斑蝥素及其纳米粒在Caco-2细胞模型中的跨膜转运机制

目的 研究乳糖化-去甲斑蝥素（Lac-NCTD）及其壳聚糖纳米粒（Lac-NCTD-NPs）的细胞摄取、转运机制。方法 采用Caco-2细胞单层模型研究Lac-NCTD和Lac-NCTD-NPs的摄取和跨膜转运；考察了时间、温度、pH值、药物质量浓度、吸收抑制剂和促进剂对药物跨膜吸收的影响，并比较两种剂型吸收过程的差异。结果 Lac-NCTD以主动转运为主要方式被细胞摄取和转运，少部分通过旁路转运。药物的摄取和时间呈正相关，与温度呈负相关。P-糖蛋白（P-gp）和多药耐药相关蛋白2（MRP2）抑制剂能增加Lac-NCTD的细胞摄取（P＜0.05）。药物从基底侧（basolateral，BL）到肠腔侧（apical，AP）的渗透系数（P_app(BL→AP)）大于P_app(AP→BL)。内吞抑制剂氧化苯砷对药物的转运无影响，旁路转运促进剂去氧胆酸钠能增加药物转运。结论 Lac-NCTD主要以主动转运方式被吸收，少部分通过旁路转运被Caco-2细胞摄取和转运，此过程受P-gp和MRP2外排蛋白作用，且药物纳米粒的摄取和转运较其溶液均有增加。

Transport mechanism of lactosyl-norcantharitin and lactosyl-norcantharitin nanoparticles across Caco-2 monolayer model

Objective To study the mechanisms of absorption and transport of lactosyl-norcantharitin (Lac-NCTD) and lactosyl-norcantharitin nanoparticles (Lac-NCTD-NPs) in intestinal membranes. Methods The Caco-2 cell monolayer model was used to study the transport mechanism of Lac-NCTD and Lac-NCTD-NPs across the membranes. The relative factors for enhancing the absorption of drug carriers, including time, temperature, pH value, drug concentration, enhancers, and inhibitors, were also investigated. The differences between Lac-NCTD and Lac-NCTD-NPs in transport of membranes were explored. Results Lac-NCTD was not only absorbed simply by active transport but also through paracellular transference as the minor. The Lac-NCTD uptake was not controlled by pH value, but positively correlated to uptake time and negatively correlated to temperature and it was also significantly enhanced by the inhibitor of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2(MRP2). Apparent permeability coefficients (P_app) of basolateral (BL) to apical (AP) was higher than that of AP to BL. Sodium deoxycholate (SDCh) slightly enhanced the drug absorption but oxophenylarsine had no effect. Conclusion The uptake and absorption of Lac-NCTD are active transport as the dominant process. P-gp and MRP2 have strong efflux effects on the uptake and transepithelial transport of Lac-NCTD. Lac-NCTD-NPs could significantly enhance the drug absorption compared with Lac-NCTD.